{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T05:52:28Z","timestamp":1785909148498,"version":"3.56.0"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:p>\n                    Obesity and high-fat diet (HFD) consumption are associated with cognitive decline and increased risk of neurodegenerative disorders, including Alzheimer\u2019s disease (AD). Gut microbiota dysbiosis is a key factor for obesity-related brain dysfunctions.\n                    <jats:italic>Opuntia ficus-indica<\/jats:italic>\n                    fruit (OFIF) has shown beneficial metabolic and neuroprotective effects, but the contribution of the gut microbiota has not been explored yet. This study investigated whether OFIF exerts neuroprotective effects in HFD mice through microbiota-dependent mechanisms. C57BL\/6 mice were fed a standard diet or HFD for 16\u202fweeks, with or without OFIF supplementation. A subgroup of HFD\u202f+\u202fOFIF mice received a broad-spectrum antibiotic cocktail to deplete gut microbiota. Metabolic parameters, cognitive performance, brain morphology, AD\u2013related gene expression (PCR array), and gut microbiota composition were assessed. OFIF supplementation improved insulin resistance in HFD-mice, also in the presence of antibiotics, suggesting microbiota-independent metabolic benefits. In contrast, OFIF prevented HFD-induced reduced brain weight, neuronal damage, and partially restored cognitive impairment, effects that were abolished following microbiota depletion. At the molecular level, OFIF modulated the expression of multiple AD-related genes in the cortex and hippocampus, including pathways involved in amyloid processing, synaptic function, and lipid metabolism. These transcriptional changes were absent in antibiotic-treated mice. Microbiota analysis revealed that OFIF positively modulated gut microbiota composition, leading to enrichment of genera such as\n                    <jats:italic>Duncaniella<\/jats:italic>\n                    and\n                    <jats:italic>Paramuribaculu<\/jats:italic>\n                    m, which positively correlated with brain structural. In conclusion, our findings suggest that microbiota is a critical mediator of OFIF-driven brain protection and supports the potential of OFIF as a dietary strategy to counteract obesity-associated cognitive decline.\n                  <\/jats:p>","DOI":"10.3389\/fnut.2026.1909657","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T05:40:05Z","timestamp":1785908405000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuroprotective effects of Opuntia ficus-indica fruit in high-fat-diet-induced obese mice: evidence for a role of the gut microbiota"],"prefix":"10.3389","volume":"13","author":[{"given":"Pasquale","family":"Calvi","sequence":"first","affiliation":[{"name":"Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo","place":["Palermo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Terzo","sequence":"additional","affiliation":[{"name":"Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo","place":["Palermo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Giardina","sequence":"additional","affiliation":[{"name":"Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo","place":["Palermo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Timeo","sequence":"additional","affiliation":[{"name":"Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo","place":["Palermo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation (IRIB)","place":["Palermo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicol\u00f2","family":"Ricciardi","sequence":"additional","affiliation":[{"name":"Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), University of Palermo","place":["Palermo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuditta","family":"Gambino","sequence":"additional","affiliation":[{"name":"Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), University of Palermo","place":["Palermo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierangelo","family":"Sardo","sequence":"additional","affiliation":[{"name":"Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), University of Palermo","place":["Palermo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Massaro","sequence":"additional","affiliation":[{"name":"Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo","place":["Palermo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Nuzzo","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation (IRIB)","place":["Palermo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"Picone","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation (IRIB)","place":["Palermo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Mul\u00e8","sequence":"additional","affiliation":[{"name":"Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo","place":["Palermo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Amato","sequence":"additional","affiliation":[{"name":"Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo","place":["Palermo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1016\/j.bbadis.2016.12.014","article-title":"Common neurodegenerative pathways in obesity, diabetes, and Alzheimer's disease","volume":"1863","author":"Pugazhenthi","year":"2017","journal-title":"Biochim Biophys Acta Mol basis Dis"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"869","DOI":"10.2174\/1567205015666180613112237","article-title":"Dietary fat intake and risk of Alzheimer\u2019s disease and dementia: a meta-analysis of cohort 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